Sorafenib prevents the proliferation and induces the apoptosis of liver cancer cells by regulating autophagy and hypoxia-inducible factor-1.
autophagy
hypoxia
hypoxia-inducible factor-1α
liver cancer
sorafenib
Journal
Experimental and therapeutic medicine
ISSN: 1792-1015
Titre abrégé: Exp Ther Med
Pays: Greece
ID NLM: 101531947
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
received:
04
05
2020
accepted:
29
03
2021
entrez:
4
8
2021
pubmed:
5
8
2021
medline:
5
8
2021
Statut:
ppublish
Résumé
Sorafenib has been approved as a systemic drug for advanced liver cancer; however, the underlying mechanisms remain unclear. The present study aimed to investigate the effects of sorafenib on the proliferation, autophagy and apoptosis of HepG2 cells under hypoxia. Briefly, reverse transcription-quantitative PCR and western blotting was performed to quantify HIF-1, LC3II/I, mTOR and p70s6K expression levels. Cell proliferation was determined using the Cell Counting Kit-8 assay and the cell apoptosis rate was evaluated using flow cytometry. The results demonstrated that autophagy and apoptosis were induced by hypoxia, and that sorafenib further enhanced hypoxia-induced autophagy and apoptosis in HepG2 cells in a dose-dependent manner. Furthermore, the mechanism of sorafenib-mediated autophagy in liver cancer cell were investigated by using chloroquine (CQ). The results showed that CQ significantly inhibited autophagy by decreasing LC3II/LC3I ratio in HepG2 cells treated with sorafenib and/or hypoxia. By contrast, sorafenib could increase the expression of hypoxia-inducible factor-1 (HIF-1) and of the autophagy marker (LC3II/I) and decrease the expression of mammalian target of rapamycin and p70 ribosomal S6 kinase in HepG2 cells under normoxia and hypoxia conditions, suggesting that sorafenib could induce hypoxia and autophagy in liver cancer cells. In addition, sorafenib was demonstrated to prevent proliferation and induce apoptosis of HepG2 cells under normoxia and hypoxia. Sorafenib could also prevent the malignant behavior of HepG2 by inducing hypoxia and autophagy. In summary, the findings from the present study suggested that sorafenib may inhibit liver cancer progression by activating autophagy and HIF-1 signaling pathway.
Identifiants
pubmed: 34345262
doi: 10.3892/etm.2021.10412
pii: ETM-0-0-10412
pmc: PMC8311259
doi:
Types de publication
Journal Article
Langues
eng
Pagination
980Informations de copyright
Copyright: © Yang et al.
Déclaration de conflit d'intérêts
The authors declare that they have no competing interests.
Références
Sci Rep. 2019 Jul 12;9(1):10147
pubmed: 31300716
Autophagy. 2011 Oct;7(10):1159-72
pubmed: 21691147
Gastroenterology. 2004 Nov;127(5 Suppl 1):S35-50
pubmed: 15508101
Oncol Rep. 2018 Dec;40(6):3235-3248
pubmed: 30272354
J Biol Chem. 2017 Feb 24;292(8):3379-3388
pubmed: 28082672
J Clin Invest. 2015 Jan;125(1):25-32
pubmed: 25654547
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Semin Nucl Med. 2015 Mar;45(2):163-76
pubmed: 25704388
Cell Death Dis. 2018 Mar 14;9(3):407
pubmed: 29540819
Int J Oncol. 2017 Jul;51(1):18-24
pubmed: 28560457
Target Oncol. 2017 Apr;12(2):243-253
pubmed: 28299600
J BUON. 2015 Jan-Feb;20(1):218-22
pubmed: 25778319
Cancer Metastasis Rev. 2007 Jun;26(2):225-39
pubmed: 17440684
BMB Rep. 2016 Aug;49(8):424-30
pubmed: 27418283
J Hepatol. 2014 Dec;61(6):1397-406
pubmed: 25157983
N Engl J Med. 2008 Jul 24;359(4):378-90
pubmed: 18650514
Autophagy. 2011 Oct;7(10):1261-2
pubmed: 21814046
Int J Oncol. 2017 Jan;50(1):297-309
pubmed: 27959383
Int J Cancer. 2012 Aug 1;131(3):548-57
pubmed: 21858812
Anticancer Res. 2010 Dec;30(12):4951-8
pubmed: 21187475
Lancet Oncol. 2009 Jan;10(1):25-34
pubmed: 19095497
Cells. 2019 Jan 01;8(1):
pubmed: 30609663
Oncol Rep. 2020 Jan;43(1):3-15
pubmed: 31746396
Nat Commun. 2017 Sep 11;8(1):517
pubmed: 28894087
Cancer. 2018 Aug;124(16):3307-3318
pubmed: 29671878
Kidney Int. 2020 Jul;98(1):234-235
pubmed: 32437765
J Hematol Oncol. 2019 Oct 26;12(1):110
pubmed: 31655607
PLoS One. 2017 Mar 21;12(3):e0174153
pubmed: 28323861
Methods Enzymol. 2017;587:71-86
pubmed: 28253977
Exp Mol Med. 2018 Oct 12;50(10):1-9
pubmed: 30315182
Cell Biol Int. 2015 Aug;39(8):891-8
pubmed: 25808799
Nat Med. 2019 Apr;25(4):620-627
pubmed: 30833748
Lancet. 2012 Dec 15;380(9859):2197-223
pubmed: 23245608
Cold Spring Harb Perspect Med. 2016 Apr 01;6(4):a026120
pubmed: 27037419
Med Res Rev. 2019 Nov;39(6):2082-2104
pubmed: 30912203
Antioxid Redox Signal. 2014 Oct 1;21(10):1516-54
pubmed: 24512032
Brain Res Bull. 2016 Jul;125:152-8
pubmed: 27320472
Mol Pharmacol. 2017 Sep;92(3):246-255
pubmed: 28242743
Surg Oncol. 2016 Jun;25(2):74-85
pubmed: 27312032
Cell Signal. 2014 Dec;26(12):2694-701
pubmed: 25173700
Int J Mol Sci. 2020 May 09;21(9):
pubmed: 32397371
Cell Signal. 2016 Jun;28(6):663-74
pubmed: 26976209
J Surg Res. 2012 Aug;176(2):542-8
pubmed: 22261591
Nat Rev Cancer. 2017 Sep;17(9):528-542
pubmed: 28751651
Biol Res. 2019 Mar 15;52(1):12
pubmed: 30876462
Oncol Lett. 2017 Jun;13(6):5028-5034
pubmed: 28599504
Rinsho Byori. 2016 Jul;64(7):787-796
pubmed: 30695467
Chin J Cancer. 2017 Jun 24;36(1):52
pubmed: 28646911
World J Gastroenterol. 2016 Nov 14;22(42):9279-9287
pubmed: 27895416
Autophagy. 2018;14(8):1435-1455
pubmed: 29940786
Cell Death Dis. 2013 Feb 07;4:e485
pubmed: 23392173
J Natl Cancer Inst. 2001 Feb 21;93(4):266-76
pubmed: 11181773
Am J Physiol Lung Cell Mol Physiol. 2001 Oct;281(4):L1021-7
pubmed: 11557606